Inhibition of cerebellar nitric oxide synthase and cyclic GMP production by melatonin via complex formation with calmodulin

David Pozo, Russel J. Reiter, Juan R. Calvo, Juan M. Guerrero

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Abstract

Constitutive rat cerebellar nitric oxide synthase (NOS) activity is shown to be inhibited by physiological concentrations of the pineal hormone melatonin. The inhibition was dose dependent and was coupled to an inhibition of the cyclic GMP production activated by L-arginine. Results also show that calmodulin appears to be involved in this process because its presence in the incubation medium was able to prevent the effect of melatonin on both NOS activity and cyclic GMP production. Moreover, polyacrylamide gel electrophoresis studies suggest that melatonin can interact with calmodulin modifying the binding of the peptide to the synthetic NOS peptide encompassing the calmodulinbinding domain of constitutive NOS from rat cerebellum, the natural mechanism by which calmodulin activates cerebellar NOS.

Original languageEnglish (US)
Pages (from-to)430-442
Number of pages13
JournalJournal of Cellular Biochemistry
Volume65
Issue number3
DOIs
StatePublished - Jun 1 1997

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Keywords

  • calmodulin
  • cerebellum
  • melatonin
  • nitric oxide
  • nitric oxide synthase
  • pineal gland

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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